Cellular retinol binding protein 1 transfection reduces proliferation and AKT-related gene expression in H460 non-small
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ORIGINAL ARTICLE
Cellular retinol binding protein 1 transfection reduces proliferation and AKT-related gene expression in H460 non-small lung cancer cells Amedeo Ferlosio1 · Elena Doldo1 · Sara Agostinelli1 · Gaetana Costanza1,2 · Federica Centofanti1 · Angelo Sidoni3 · Augusto Orlandi1,4,5 Received: 10 March 2020 / Revised: 13 August 2020 / Accepted: 28 August 2020 © The Author(s) 2020
Abstract In recent years, new treatments with novel action mechanisms have been explored for advanced non-small cell lung cancer (NSCLC). Retinoids promote cancer cell differentiation and death and their trafficking and action is mediated from specific cytoplasmic and nuclear receptors, respectively. The purpose of this study was to investigate the effect of Cellular retinol binding protein-1 (CRBP-1) transfection in H460 human NSCLC cell line, normally not expressing CRBP-1. H460 cells were transfected by using a vector pTargeT Mammalian expression system carrying the whole sequence of CRBP-1 gene. For proliferation and apoptosis studies, cells were treated with different concentrations of all-trans Retinoic Acid (atRA) and retinol. AKT-related gene expression was analyzed by using western blot and Signosis array and results analysed by one-way analysis of variance (ANOVA) or by t-student test. CRBP-1+ showed reduced proliferation and viability in basal condition and after atRA treatment when compared to empty-transfected H460 cells. Reduced proliferation in CRBP-1 + H460 cells associated to the down-regulation of pAKT/pERK/pEGFR-related genes. In particular, gene array documented the down-regulation of AKT and Stat-3-related genes, including M-Tor, Akt1, Akt2, Akt3, Foxo1, p27, Jun. Restoration of CRBP-1 expression in H460 cells reduced proliferation and viability in both basal condition and after atRA treatment, likely by down-regulating AKT-related gene level. Further studies are needed to better clarify how those CRBP-1-related intracellular pathways contribute to counteract NSCLC progression in order to suggest a potential tool to improve efficacy of retinoid anti lung cancer adjuvant therapy. Keywords Non-small cell lung cancer · CRBP-1 · AKT pathway · Retinoids
Introduction Amedeo Ferlosio and Elena Doldo have equally contributed as first authors. * Augusto Orlandi [email protected] 1
Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy
2
Dermapathology laboratory, San Gallicano Institute, Rome, Italy
3
Department of Experimental Medicine, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, Perugia, Italy
4
Department of Anatomic Pathology, Tor Vergata Policlinic of Rome, Rome, Italy
5
Institute of Anatomic Pathology, Dept. of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy
Lung cancer is the first cause of neoplastic death worldwide in both men and women population [1]. Non-small cell lung carcinoma (NSCLC) accounts for 80% of all cases. Nevertheless the recent progr
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